U.S. patent number 5,906,599 [Application Number 08/552,467] was granted by the patent office on 1999-05-25 for device for delivering biological agents.
This patent grant is currently assigned to InterMED, Inc.. Invention is credited to Antoine Kaldany.
United States Patent |
5,906,599 |
Kaldany |
May 25, 1999 |
Device for delivering biological agents
Abstract
A device for delivering biological agents includes a cannula for
insertion into tissue having a distal end with a notch formed
therein. A flexible membrane extending across the cannula notch has
a surface for supporting a quantity of a biological agent. A
displacement member is disposed within the cannula for displacing
the support surface of the membrane laterally with respect to the
cannula to deliver the biological agent with precision to a tissue
site or body cavity.
Inventors: |
Kaldany; Antoine (Chestnut
Hill, MA) |
Assignee: |
InterMED, Inc. (Chestnut Hill,
MA)
|
Family
ID: |
24205465 |
Appl.
No.: |
08/552,467 |
Filed: |
November 9, 1995 |
Current U.S.
Class: |
604/264; 604/57;
604/58; 604/60; 604/506 |
Current CPC
Class: |
A61D
7/00 (20130101); A61M 37/0069 (20130101); A61B
2090/3987 (20160201); A61B 2017/00539 (20130101) |
Current International
Class: |
A61D
7/00 (20060101); A61M 005/00 (); A61M 025/00 ();
A61M 031/00 () |
Field of
Search: |
;604/48,49,51,52,57-60,68,70,72,93,95,158-160,164-166,170,264
;606/13-15 |
References Cited
[Referenced By]
U.S. Patent Documents
Foreign Patent Documents
|
|
|
|
|
|
|
0207726 |
|
Jul 1987 |
|
EP |
|
91/10399 |
|
Jul 1991 |
|
WO |
|
Primary Examiner: Coggins; Wynn Wood
Assistant Examiner: Sadula; Jennifer R.
Attorney, Agent or Firm: Hamilton, Brook, Smith &
Reynolds, P.C.
Claims
What is claimed is:
1. A biological agent delivery device comprising:
a cannula having a longitudinally extending wall and a rigid closed
pointed tip at a distal end with a notch in said wall near the
distal end forming a lateral opening in the cannula wall;
a flexible membrane having a lateral support surface for supporting
a biological agent, the membrane being disposed within the cannula
notch, the support surface forming a laterally facing pouch capable
of being displaced laterally inwardly and outwardly within the
cannula notch for containing and laterally displacing the
biological agent; and
a displacement member disposed within the wall of the cannula for
displacing the support surface of the membrane laterally with
respect to the cannula to deliver the biological agent.
2. The delivery device of claim 1 further comprising an outer tube
mounted concentric with the cannula for relative movement with
respect to the cannula or enclosing or exposing the cannula
notch.
3. The delivery device of claim 1 in which the displacement member
comprises a piston.
4. The delivery device of claim 1 in which the displacement member
comprises a volume of fluid.
5. The delivery device of claim 4 in which the fluid is a
liquid.
6. The delivery device of claim 4 in which the fluid is a gas.
7. The delivery device of claim 1 in which the support surface
forms a pouch when the flexible membrane is in a non-displaced
state.
8. The delivery device of claim 7 in which the pouch is
preformed.
9. The delivery device of claim 1 in which the flexible membrane
extends within the cannula and comprises a tubular member having a
closed distal end, the support surface of the membrane being
located near said closed distal end and positioned within the
cannula notch.
10. The delivery device of claim 1 further comprising fiber optics
within the cannula for delivering radiation to a desired tissue
site.
11. The delivery device of claim 10 further comprising a lens
associated with the fiber optics for enabling viewing of regions
external to the cannula.
12. A biological agent delivery device comprising:
a cannula having a longitudinally extending wall and a rigid closed
pointed tip at a distal end with a notch in said wall near the
distal end forming a lateral opening in the cannula wall;
a flexible membrane having a lateral support surface for supporting
a biological agent, the membrane being disposed within the cannula
notch, the support surface forming a laterally facing pouch capable
of being displaced laterally inwardly and outwardly within the
cannula notch for containing and laterally displacing the
biological agent; and
a displacement member disposed within the wall of the cannula for
displacing the support surface of the membrane laterally with
respect to the cannula to displace the biological agent; and
an outer tube mounted concentric with the cannula for relative
movement with respect to the cannula for enclosing or exposing the
cannula notch.
13. The delivery device of claim 12 in which the displacement
member comprises a piston.
14. The delivery device of claim 12 in which the displacement
member comprises a volume of fluid.
15. The delivery device of claim 14 in which the fluid is a
liquid.
16. The delivery device of claim 14 in which the fluid is a
gas.
17. The delivery device of claim 12 in which the support surface
forms a pouch when the flexible membrane is in a non-displaced
state.
18. The delivery device of claim 17 in which the pouch is
preformed.
19. The delivery device of claim 12 in which the flexible membrane
extends within the cannula and comprises a tubular member having a
closed distal end, the support surface of the membrane being
located near said closed distal end and positioned within the
cannula notch.
20. The delivery device of claim 12 further comprising fiber optics
within the cannula for delivering radiation to a desired tissue
site.
21. The delivery device of claim 20 further comprising a lens
associated with the fiber optics for enabling viewing of regions
external to the cannula.
22. A method of delivering a biological agent to a tissue site
comprising the steps of:
providing a cannula having a longitudinally extending wall and a
rigid closed pointed tip at a distal end with a notch in said wall
near the distal end forming a lateral opening in the cannula
wall;
supporting a biological agent on a lateral support surface of a
flexible membrane, the membrane being disposed within the cannula
notch, the support surface forming a laterally facing pouch capable
of being displaced laterally inwardly and outwardly within the
cannula notch for containing and laterally displacing the
biological agent;
inserting the distal end of the cannula into the tissue site;
and
laterally displacing the support surface of the membrane with
respect to the cannula with a displacement member disposed within
the wall of the cannula to deliver the biological agent to the
tissue site.
23. The method of claim 22 further comprising the step of enclosing
the cannula notch with an outer tube mounted concentric with the
cannula before insertion of the distal end of the cannula into the
tissue site.
24. The method of claim 23 further comprising the step of extending
the cannula to expose the cannula notch beyond the outer tube after
insertion of the distal end of the cannula into the tissue
site.
25. The method of claim 22 further comprising the step of extending
the flexible membrane within the cannula, the membrane comprising a
tubular member having a closed distal end, the support surface of
the membrane being located near said closed distal end and
positioned within the cannula notch.
26. The method of claim 22 further comprising the step of
delivering radiation to a desired tissue site with fiber
optics.
27. The method of claim 22 further comprising the step of viewing
regions external to the cannula with fiber optics.
28. The method of claim 22 further comprising the step of forming
the support surface of the flexible membrane into a pouch.
29. A subcutaneous delivery device comprising:
a cannula having a longitudinally extending wall and a rigid closed
pointed tip at a distal end with a notch in said wall near the
distal end forming a lateral opening in the cannula wall;
a flexible membrane having a lateral support surface supporting a
product to be delivered, the membrane being disposed within the
cannula notch, the support surface forming a laterally facing pouch
capable of being displaced laterally inwardly and outwardly within
the cannula notch for containing and laterally displacing the
biological agent; and
a displacement member disposed within the wall of the cannula for
displacing the support surface of the membrane laterally with
respect to the cannula to deliver the product.
Description
BACKGROUND
Much effort has been expended in recent years to find an effective
and superior way of administering drugs to patients' bodies.
Products such as the transdermal patch and once-a-day orally
administered pills that more precisely deliver drugs have been
developed. Such products are a boon to patients for they boost the
effectiveness of the drugs and limit side effects by precisely
controlling how quickly drugs are released in the body; by keeping
drugs at a constant level and by delivering them exactly where
needed.
One such development is the injection or implantation of drugs in
the form of in microscopic particles or pellets at a disease site.
The drugs are encapsulated in polymers or fatty compounds, such as
liposomes which permit slow release of the encapsulated drug over
time thereby potentially lowering the drugs toxicity.
In addition, there are times when it is desirable to deliver a
biological agent that is in a non-conventional form to a disease
site such as a drug in a loose particulate form, or a quantity of
cells, cell clusters or cellular extracts in a biocompatible
solution. A particulate biological agent can be in a granular,
powdered, or microsphere form. The problem with biological agents
in these forms is that they are difficult to properly deliver to a
diseased tissue site.
SUMMARY OF THE INVENTION
The present invention provides a novel device with a distal end
insertable into the tissue or a body cavity of a patient for
delivering both particulate and liquid biological agents in a
quick, predictable, safe and easy manner without damaging the
biological agent. This is important in the delivery of cells or
microspheres. The biological agent delivery device includes a
cannula having a longitudinally extending wall and a distal end
with a notch opening formed in the wall near the distal end. A
flexible membrane disposed within the cannula notch opening has a
support/delivery surface for supporting a quantity of a biological
agent. A displacement member is disposed within the wall of the
cannula for axial movement therein to laterally displace the
support surface of the flexible membrane to deliver the biological
agent to the desired tissue site.
In preferred embodiments, the present invention biological agent
delivery device further includes an outer tube mounted concentric
with the cannula. The cannula is capable of sliding within the
outer tube to retract or extend the cannula relative to the outer
tube for enclosing the cannula notch within the outer tube for
insertion into tissue or exposing the cannula notch beyond the
outer tube to allow delivery of the biological agent after
insertion into tissue. The flexible membrane is preferably a
tubular member having a closed terminal end which extends within
the cannula, with the support surface of the flexible membrane
being located near the closed terminal end and positioned within
the cannula notch. When the flexible membrane is in a non-displaced
state, the support surface is indented into the flexible membrane
to form a pouch. This pouch can optionally be preformed. The
displacement member in one preferred embodiment is a piston which
moves axially within the cannula for displacing the support
surface. In another preferred embodiment, the displacement member
is a fluid such as a liquid or a gas.
In still another preferred embodiment, the present invention
biological agent delivery device is a flexible catheter with fiber
optics being optionally provided within the cannula for delivering
radiation to a desired tissue or body cavity site. A lens
associated with the fiber optics enables viewing of regions
external to the cannula.
BRIEF DESCRIPTION OF THE DRAWINGS
The foregoing and other objects, features and advantages of the
invention will be apparent from the following more particular
description of preferred embodiments of the drawings in which like
reference characters refer to the same parts throughout the
different views. The drawings are not necessarily to scale,
emphasis instead being placed upon illustrating the principles of
the invention.
FIG. 1 is a plan view of the present invention biological agent
delivery device.
FIG. 2 is a side sectional view of the present invention biological
agent delivery device with the distal end of the device inserted
into tissue.
FIG. 3 is a side sectional view of the distal end of the biological
agent delivery device with the outer tube 102 retracted to expose
the cannula notch 104b and the support surface 105a of the flexible
membrane 105.
FIGS. 4 and 5 are side sectional views of the distal end of the
biological agent delivery device of FIG. 2 depicting the delivery
of a quantity of a biological agent to a tissue site.
FIGS. 6 and 7 are side sectional views of the distal end of another
preferred biological agent delivery device depicting the delivery
of a quantity of a biological agent to a tissue site.
FIG. 8 is a side sectional view of the distal end of yet another
preferred biological agent delivery device.
FIG. 9 is a side sectional view of the distal end of still another
preferred biological agent delivery device.
FIG. 10 is a side sectional view of the distal end of still another
preferred biological agent delivery device.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
Referring to FIGS. 1 and 2, biological agent delivery device 100 is
an apparatus suitable for single-handed subcutaneous delivery of a
biological agent 106 such as a quantity of a loose particulate
drug, or a quantity of cells, cell clusters or cellular extracts in
solution with a biological compatible carrier. For purposes of
illustrating the invention, we have selected a delivery device
similar to the device disclosed in U.S. patent application Ser. No.
08/271,148 filed Jul. 6, 1994 which is incorporated herein by
reference in its entirety. However, other mechanisms for inserting
and retracting the various members may substitute therefore.
Additionally, for illustration purposes, the biological agent 106
depicted in the drawings is a particulate drug.
Delivery device 100 has a housing 12 with a pair of finger grips 14
extending transverse the longitudinal axis of the housing. A
driving member 16 is slideably engaged with a track 20 formed along
the longitudinal length of housing 12. The housing 12 has an
external cylindrical bore 18 formed therein which extends along the
longitudinal axis of the housing 12. A tubular member or cannula
104, having an internal bore 104c is mounted within the external
cylindrical bore 18 and extends along the longitudinal axis of bore
18. A piston 108 is shown disposed within internal bore 104c.
Cannula 104 has a solid distal tip 104a which is angled for
penetration into tissue. A radially lateral opening in the cannula
104 near tip 104a forms a cannula notch 104b (FIG. 3). An outer
tube 102 is secured to housing 12 and is mounted concentrically
about cannula 104. Cannula 104 is axially slideable relative to
cylindrical bore 18 and outer tube 102 for extending or retracting
cannula 104 relative to outer tube 102 in order to enclose or
expose cannula notch 104b. A flexible membrane 105 having a
collapsible support surface 105a, a tubular portion 105b and a
closed distal end 105c is positioned coaxially within bore 104c of
cannula 104. The distal end 105c of membrane 105 extends into
cannula notch 104b and abuts the distal end 103 of cannula notch
104b. Flexible membrane 105 extends across the opening of cannula
notch 104b and prevents bore 104c from communicating with regions
outside cannula 104 through cannula notch 104b. Piston 108 is
mounted coaxially within the tubular portion 105b of the flexible
membrane 105. Piston 108 is axially slideable relative to cannula
104 and tubular portion 105b and acts as a displacement member for
radially, laterally displacing support surface 105a. Since the bore
104c within cannula 104 terminates at the distal end 103 of cannula
notch 104b, piston 108 is restricted from extending past cannula
notch 104b.
The support surface 105a of flexible membrane 105 is located near
the distal end 105c of the membrane 105 for supporting a quantity
of a biological agent 106. The support surface 105a is changeable
from an undisplaced or collapsed position to a displaced position.
When membrane 105 is an undisplaced position, support surface 105a
is indented downwardly (or inwardly) into flexible membrane 105 to
form a pouch with support surface 105a contacting the opposite side
of the membrane 105. The pouch is typically formed by pushing
support surface 105a downwardly (inwardly). The support surface
105a provides the surfaces of the pouch. Alternatively, the pouch
can be preformed into membrane 105 such as by molding. When
membrane 105 is in a displaced position, the pouch disappears with
the support surface 105a being relatively horizontal. Membrane 105
is preferably formed from a flexible polymeric material which can
either be stretchable or non-stretchable and can be transparent.
Alternatively, membrane 105 can also be formed from other suitable
flexible materials such as fabrics. Although tubular portion 105b
is typically flexible, alternatively, tubular portion 105b can be
rigid with only the support surface 105a being flexible.
The piston 108 and cannula 104 are secured at their respective
proximal ends by a piston grip 48, and a cannula grip 50. The
proximal end of tubular portion 105b of membrane 105 of has a
flange 105d which secures tubular portion 105b to cannula 104 at
the proximal end of cannula grip 50. Additionally, if needed,
tubular portion 105b can be bonded within bore 104c with an
adhesive. The piston grip 48 and cannula grip 50 are disc-shaped
with a diameter which approximates the diameter of the cylindrical
bore. The piston grip 48 and the cannula grip 50 are slideably
engaged within the housing bore 18. The piston grip 48 and cannula
grip 50 have respective channels formed therein through which drive
pins 32 and 34 respectively extend for engagement with the proximal
ends of the piston 108 and cannula 104 respectively.
Piston drive pin 32 and cannula drive pin 34 both extend through a
single elongate slot 128 in housing 12. Housing slot 128 has a
notch 128a located at its distal end for engaging cannula drive pin
34 when cannula drive pin 34 is in the advanced position. Piston
drive pin 32 extends through driving member 16 through a hole 32a.
Cannula drive pin 34 extends through driving member 16 through an
elongate driving member slot 126. Driving member slot 126 has a
notch 126a located at its distal end for engaging cannula drive pin
34.
The piston 108, cannula 104 and outer tube 102 are preferably
formed of rigid sterilizable material such as stainless steel.
Other components of the device, including the housing, driving
member, piston and cannula grips, etc. are preferably made from low
cost plastic material. The use of molded plastic components for the
manufacture of the instrument is preferred to lower the cost so
that the device can be disposed of after use.
In operation, in order to subcutaneously deliver a quantity of a
biological agent 106 to a desired tissue site, the surface 112a of
tissue 112 is first cut with a scalpel. The tip 104a of cannula 104
is then inserted into the incision within tissue 112 while driving
member 16 is in a retracted position and the distal end 101 of
delivery device 100 is advanced into tissue 112 until reaching a
desired location. When driving member 16 is in a retracted
position, cannula notch 104b is enclosed by outer tube 102 with the
tip of piston 108 being at the proximal end of cannula notch 104b.
Outer tube 102 protects the biological agent 106 and prevents it
from spilling out of cannula notch 104b prematurely. Alternatively,
tip 104a of cannula 104 can be inserted into tissue 112 by
puncturing the surface 112a of tissue 112 with tip 104a.
Driving member 16 is then moved distally along track 20 toward the
distal end 101 of delivery device 100. Cannula drive pin 34 is
engaged within notch 126a of driving member slot 126 and piston
drive pin 32 is engaged by hole 32a. As the driving member 16 is
advanced, cannula 104 is extended from outer tube 102 such that
cannula notch 104b and the biological agent 106 are exposed beyond
the tip 102a of outer tube 102 as seen in FIG. 4. At the same time,
driving member 16 advances piston 108 by engaging piston drive pin
32 with hole 32a such that the cannula 104 and the piston 108
advance together in unison. Cannula 104 is extended until cannula
drive pin 34 reaches the distal end of housing slot 128 where
cannula drive pin 34 engages housing slot notch 128a.
As driving member 16 is further advanced, cannula drive pin 34
disengages from notch 126a in driving member slot 126 and piston
drive pin 32 is advanced further, thereby advancing piston 108
forward relative to cannula 104. As piston 108 is extended into
cannula notch 104b, piston 108 laterally displaces the support
surface 105a of membrane 105 thereby laterally displacing the
biological agent 106 from cannula notch 104b into the surrounding
tissue 112 as seen in FIG. 5. Piston 108 is extended into cannula
notch 104b until the proximal end of driving member slot 126
reaches cannula drive pin 34, thereby preventing further
advancement of driving member 16. Further advancement of piston 108
is also prevented by the distal end 103 of cannula notch 104b.
Once the biological agent 106 is deposited into tissue 112, the
distal end 101 of delivery device 100 can be removed from tissue
112. To remove distal end 101 from the tissue 112, the cannula 104
and the piston 108 are first retracted relative to outer tube 102
by retracting driving member 16. This leaves behind the biological
agent 106 within tissue 112. Distal end 101 of delivery device 100
is then pulled from tissue 112 leaving behind a small puncture
wound.
FIGS. 6 and 7 depict the distal end of biological agent delivery
device 130 which is another preferred embodiment of the present
invention differing from delivery device 100 in that piston 108 and
the components associated with advancing and retracting piston 108
are omitted. Instead, in order to deliver a biological agent 106, a
fluid 107a such as a gas or a liquid is introduced into cavity 107
within membrane 105 to serve as a displacement member in order to
laterally displace the support surface 105a. If desired, the fluid
can outwardly displace support surface 105a past the outer surface
of cannula 104 thereby forming an outward bulge in membrane 105.
The fluid is preferably air if a gas is employed or saline solution
if a liquid is employed and is preferably introduced into cavity
107 by a piston/plunger type mechanism or a closed loop pump
mechanism within or attached to delivery device 130. Such a
mechanism can be a syringe-type device or a calibrated ampoule-type
device. Alternatively, the fluid can be introduced from a reservoir
by a pump or from a pressurized tank and can be any other suitable
gas or liquid.
Referring to FIGS. 8 and 9, flexible membrane 117 differs from
flexible membrane 105 in that it does not include a tubular portion
105b but consists of a flexible membrane extending across and
sealed over the lateral opening of cannula notch 104b. As a result,
in the embodiment shown in FIG. 8, the piston 108 contacts and
slides within bore 104c of cannula 104. In the embodiment depicted
in FIG. 9, the support surface 105a of membrane 117 is laterally
displaced by a fluid such as gas or liquid introduced into bore
104c of cannula 104.
Referring to FIG. 10, biological agent delivery device 132 is a
flexible catheter for insertion into body cavities of a patient. In
order to provide flexibility of the catheter, the cannula 104 and
outer tube 102 are made of flexible material. As in delivery device
130, the support surface 105a of flexible membrane 105 is displaced
by fluid introduced into cavity 107. Cannula 104 has a blunt tip
115 to facilitate the passage of delivery device 132 through body
cavities. Although delivery device 132 is shown to include flexible
membrane 105, alternatively, flexible membrane 117 may be employed
instead.
An optional fiber optic bundle 109 including optical fibers 109a,
109b and 109c is positioned within bore 104c of cannula 104
alongside tubular portion 105b of membrane 105. Optical fiber 109c
is directed laterally with respect to cannula 104 to provide light
to a desired drug delivery site for optimized drug absorption.
Illumination is also useful when delivering cells, subcellular
extracts, plasmids or gene products for genetic therapy because it
facilitates gene transfer. In addition, other forms of
electromagnetic radiation can be delivered by optical fiber 109c,
for example, ultra-violet light for altering cell membranes or for
sterilization, or to increase cell membrane permeability with blue
light. Furthermore, optics for viewing the delivery site are
provided by laterally positioning optical fiber 109b and lens 111.
Finally, optics for forward viewing are provided by optical fiber
109a and lens 113.
Although the present invention biological agent delivery device has
been described for primarily delivering particulate or liquid
biological agents, biological agents in pellet form can also be
delivered. The term "biological agent" is meant to encompass any
substance that can be introduced into tissue or a body cavity for
treating a patient such as drugs, microspheres, cells, cell
clusters, cells transfected with foreign DNA, cellular components,
cellular extracts or gene products. The term "drug" as used herein
is intended to have a broad construction so as to include any type
of medication capable of being administered in the manner described
herein. When biological agents in a liquid form are delivered, a
sealing arrangement can be provided around cannula notch 104b to
reduce the possibility that liquid will not leak prematurely from
cannula notch 104b when outer tube 102 encloses cannula notch
104b.
Equivalents
While this invention has been particularly shown and described with
references to preferred embodiments thereof, it will be understood
by those skilled in the art that various changes in form and
details may be made therein without departing from the spirit and
scope of the invention as defined by the appended claims. For
example, other mechanisms can be employed for advancing and
retracting cannula 104 and piston 108. Such mechanisms can include
motor or hand-operated gears and power screws, or fluid operated
cylinders. In addition, the present invention delivery device can
be employed for implanting non-therapeutic, solid or rigid objects
into tissue or body cavities such as tracking devices, radio
transmitters or pumps.
* * * * *